The mechanisms by which phagocytic cells (including granulocytes, monocytes and macrophages) function to protect the human host from bacterial and fungal infection and their alteration in various pathologic states remains the concern of the present investigations. Information will be gathered by several approaches including: 1) screening individuals with a history of repeated pyogenic infections for leukocyte functional defects and further characterizing these as indicated; 2) examining the mechanisms involved in the production and utilization of microbicidal products of the phagocytic respiratory burst, in particular superoxide and H2O2, by these cells. Particular attention will be paid to elucidating the mechanisms involved in oxidase activation following appropriate stimulation of the phagocytic cell surface as well as to discerning the nature and cellular location of the critical oxidase(s) involved in the respiratory burst. Studies on cells from normal subjects will be extended to patients with defective oxidase activity (chronic granulomatous disease of childhood) in order to define and perhaps correct their disorder in vitro and, ultimately, in vivo; 3) the potential role of oxidase-mediated mechanisms in the microbicidal and cytocidal activity of human macrophages will be examined by comparative studies with their precursor monocytes and granulocytes; 4) the mechanism by which phagocytic cells become oriented and move in a chemotactic gradient and the resultant polarization of structure and function which occurs will be explored using both normal cells and those from patients with chemotactic disorders. The purpose of these investigations is to provide a better understanding of the normal microbicidal and cytocidal mechanisms of granulocytes and macrophages, and to determine how they are altered in pathologic states characterized by abnormal defense against infection or inflammation. Such knowledge could lead to the development of means to augment or modify these mechanisms when indicated and to correct abnormalities in specific disease states.